chr3-61086761-C-G

Variant names:

• chr3-61086761-C-G
• rs7646887
• NM_002012.4:c.-163-44662G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002012.4(FHIT):​c.-163-44662G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 152,072 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.040 (214 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 1 publications found

Genes affected

FHIT (HGNC:3701): (fragile histidine triad diadenosine triphosphatase) The protein encoded by this gene is a P1-P3-bis(5'-adenosyl) triphosphate hydrolase involved in purine metabolism. This gene encompasses the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and aberrant transcripts. In fact, aberrant transcripts from this gene have been found in about half of all esophageal, stomach, and colon carcinomas. The encoded protein is also a tumor suppressor, as loss of its activity results in replication stress and DNA damage. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002012.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIT	NM_002012.4	MANE Select	c.-163-44662G>C		intron	N/A	NP_002003.1
	FHIT	NM_001166243.3		c.-163-44662G>C		intron	N/A	NP_001159715.1
	FHIT	NM_001320899.2		c.-163-44662G>C		intron	N/A	NP_001307828.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIT	ENST00000492590.6	TSL:1 MANE Select	c.-163-44662G>C		intron	N/A	ENSP00000418582.1
	FHIT	ENST00000476844.5	TSL:1	c.-163-44662G>C		intron	N/A	ENSP00000417557.1
	FHIT	ENST00000490952.1	TSL:1	n.457+78814G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 6070 AN: 151954 Hom.: 211 Cov.: 32

Gnomad AFR AF: 0.0913

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0175

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0411

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0401 AC: 6092 AN: 152072 Hom.: 214 Cov.: 32 AF XY: 0.0392 AC XY: 2914 AN XY: 74362

African (AFR) AF: 0.0916 AC: 3801 AN: 41500

American (AMR) AF: 0.0195 AC: 298 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0179 AC: 86 AN: 4802

European-Finnish (FIN) AF: 0.0207 AC: 219 AN: 10604

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0225 AC: 1532 AN: 67944

Other (OTH) AF: 0.0407 AC: 86 AN: 2112

Alfa AF: 0.00790 Hom.: 2

Bravo AF: 0.0422

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.44
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7646887; hg19: chr3-61072434;